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Title: Electrophysiological characterization of a mouse deficient for oligophrenin-1 : a mouse model of X-linked mental retardation
Author: Saintot, Pierre-Philippe
ISNI:       0000 0004 2686 9804
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2010
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Mental retardation is the most common brain disease. One of the first genes identified in X-linked mental retardation (XLMR) was the OPHN-1 gene. Mutation of this gene has been described in patients with moderate to severe cognitive impairments. MR is characterized by reduced cognitive function with or without other clinical features, thus providing a direct approach to study the neurobiology of cognition and pathogenesis of MR. I propose in this thesis to clarify the underlying mechanisms responsible for the learning impairments. My first approach was to investigate the functioning of a neuronal population using extracellular recording of fast oscillations which are thought to underlie higher cognitive performance. I showed that \(Ophn-1\) null mice displayed weaker gamma oscillations. Thereafter, Investigation of the synaptic properties of CA3 pyramidal neurons using the patch-clamp technique has been undertaken. I have shown reduced inputs of excitatory and inhibitory neurotransmission to CA3 pyramidal neurons accompanied with reduced frequency dependent facilitation of the inhibitory neurotransmission at 33Hz. Finally, a reduction in readily releasable pool size in inhibitory synapses of CA3 area was unravelled. This defect explained the reduction of frequency of sIPSCs and consequently the reduction in gamma oscillations power in Ophn-1\(^{-/y}\) slices.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry